1. Epidemiology and Global Health
  2. Medicine
Download icon

SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung

  1. Alan E Mast
  2. Alisa S Wolberg
  3. David Gailani
  4. Michael R Garvin
  5. Christiane Alvarez
  6. J Izaak Miller
  7. Bruce Aronow
  8. Daniel Jacobson  Is a corresponding author
  1. Versiti Blood Research Institute, Department of Cell Biology Neurobiology and Anatomy Medical College of Wisconsin, United States
  2. Department of Pathology and Laboratory Medicine and UNC Blood Research Center, United States
  3. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, United States
  4. Oak Ridge National Laboratory, Biosciences Division, United States
  5. University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, United States
  6. Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, United States
  7. University of Cincinnati, United States
  8. University of Tennessee Knoxville, Department of Psychology, United States
Research Article
Cite this article as: eLife 2021;10:e64330 doi: 10.7554/eLife.64330
2 figures, 2 tables and 1 additional file

Figures

Transcriptional changes in lung induced by COVID-19 infection did not alter F3, but decreased aPC anticoagulant capacity, suggesting decreased inhibition of the propagation phase of coagulation.

Figure shows differential gene expression (log2 fold change) of coagulation pathway transcripts in BALF of COVID-19 patients; the image illustrates mechanistic relationships of the protein products of the identified transcripts during coagulation. Shading indicates relative expression in COVID-19 patients compared to controls: increased (red) or decreased (blue). There was minimal change in F3 (encoding tissue factor ) and increased TFPI (encoding the major inhibitor of tissue factor activity). There was decreased THBD, PROCR, and PROS1 (encoding proteins that enhance anticoagulant activity) and increased SERPINA5 (encoding protein C inhibitor). There was also decreased SERPING1 (encoding C1-Inhibitor). Other transcripts showing changes (e.g., F11, F10, F7, F2) encode proteins typically produced in the liver; local expression of these proteins is unclear.

Transcriptional changes in lung induced by COVID-19 infection decreased PLAU and PLAUR, suggesting diminished fibrinolytic activity.

Figure shows differential gene expression (log2 fold change) of fibrinolytic pathway transcripts in BALF of COVID-19 patients; the image illustrates mechanistic relationships of the protein products of the identified transcripts during fibrinolysis. Shading indicates relative expression in COVID-19 patients compared to controls: increased (red) or decreased (blue). There was a moderate increase in PLAT (encoding tPA). There was also enhanced expression of FGB, FGA, and FGG (encoding fibrinogen chains) and decreased expression of PLAU and PLAUR (encoding uPA and uPAR, respectively). Other transcripts showing changes (e.g., F2, PLG) encode proteins typically produced in the liver; local expression of these proteins is unclear.

Tables

Table 1
Differentially expressed coagulation genes.
GeneProtein productMean COVID-19Mean controlFold changeLog2FCFDR
A2Mα2-Macroglubulin3.9177.6−43.5−5.45.2E-15
BDKRB1Bradykinin receptor B13.30.0258.98.04.3E-91
BDKRB2Bradykinin receptor B28.90.249.15.61.9E-40
F13A1Factor XIII-A subunit2.59.2−3.6−1.82.6E-05
F13BFactor XIII-B subunit0.60.0117.86.92.7E-31
F12Factor XII0.53.2−4.4−2.15.7E-10
F11Factor XI6.60.181.26.37.9E-79
F10Factor X3.20.0169.97.47.9E-140
F9Factor IX0.90.0189.67.62.2E-39
F8Factor VIII3.915.8−4.6−2.21.6E-40
F7Factor VII10.10.0363.58.52.9E-73
F5Factor V9.76.81.40.50.13
F3Tissue Factor4.23.8-1.0-0.011
F2Prothrombin0.90.0188.87.67.8E-67
FGAFibrinogen Aα chain3.40.0322.58.33.4E-206
FGBFibrinogen Bβ chain3.70.0303.98.22.4E-151
FGGFibrinogen γ chain0.70.085.46.44.8E-17
KLKB1Kallikrein B11.31.8−1.4−0.52.1E-01
KNG1Kininogen3.30.0190.77.64.2E-163
PLATTissue plasminogen activator1.80.45.32.47.1E-24
PLAUUrokinase3.8158.3−37.1−5.28.2E-172
PLAURUrokinase receptor6.2313.3−42.1−5.46.4E-286
PLGPlasminogen2.20.075.36.27.3E-38
PROCProtein C2.00.0226.57.84.1E-158
PROCREndothelial protein C receptor1.757.9−33.8−5.11.9E-50
PROS1Protein S3.2195.3−54.2−5.81.1E-174
SERPINA5Protein C Inhibitor2.70.0786.89.65.4E-145
SERPINB2Plasminogen activator inhibitor-21.00.52.31.22.1E-01
SERPINC1Antithrombin1.90.113.63.83.1E-31
SERPIND1Heparin cofactor II3.00.094.06.62.2E-72
SERPINE1Plasminogen activator inhibitor-12.75.3−1.8−0.98.8E-02
SERPINF2α2-antiplasmin5.48.2−1.4−0.51.1E-02
SERPING1C-1 inhibitor23.31923.2−80.1−6.35.4E-33
TFPITissue factor pathway inhibitor3.40.47.72.98.7E-19
THBDThrombomodulin9.6224.0−22.2−4.53.2E-48
VWFVon Willebrand factor14.57.72.01.02.0E-05
Table 2
Clinical data for patients from which BALF was extracted and analyzed for this study.
GISAID accessionIsolateNCBI accessionSRA accessionsSwab dateAgeSexPatient noDate onsetSymptoms_admissionStatus 1/13/20Diagnosis history
EPI_ISL_402127WIV02MN996527SRR11092058, SRR1109206312/30/1932MaleICU-0412/19/19Fever, cough, dyspneaFever, intermitttent coughNegative
EPI_ISL_402124WIV04MN996528SRR11092057, SRR1109206212/30/1949FemaleICU-0612/27/19Fever (37.9C), palpitationFever, malaise, coughCoronavirus (nt)
EPI_ISL_402128WIV05MN996529SRR1109206112/30/1952FemaleICU-0812/22/19Fever (38C), expectoration, malaise, dyspneaRecovered, dishargedStreptococcus pneumoniae (nt)
EPI_ISL_402129WIV06MN996530SRR11092056, SRR1109206012/30/1940MaleICU-0912/28/20Fever (38C), expectorationFever (38C), expectoration, dizzinessNegative
EPI_ISL_402130WIV07MN996531SRR11092059, SRR1109206412/30/1956MaleICU-1012/20/19Fever, dyspnea, chest tightnessFever, malaise, cough, dyspneaNegative

Additional files

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)